Strategies for multilocus linkage analysis in humans.

TLDR

The growing catalog of human DNA polymorphisms will soon enable the construction of fine genetic maps of human chromosomes. The study seeks to reexamine family‑based linkage analysis methods and to introduce a location‑score approach for efficiently detecting linkage between disease loci or new markers and established linkage groups. To this end, the authors developed the computer program LINKAGE for multilocus linkage analysis. Comparisons of two‑point and three‑point linkage tests, application of the location‑score method to simulated Duchenne muscular dystrophy pedigrees, and use of a common reference panel demonstrate that appropriate linkage‑detection strategies can markedly improve mapping efficiency and economy.

Abstract

The increasing number of DNA polymorphisms characterized in humans will soon allow the construction of fine genetic maps of human chromosomes. This advance calls for a reexamination of current methodologies for linkage analysis by the family method. We have investigated the relative efficiency of two-point and three-point linkage tests for the detection of linkage and the estimation of recombination in a variety of situations. This led us to develop the computer program LINKAGE to perform multilocus linkage analysis. The investigation also enables us to propose a method of location scores for the efficient detection of linkage between a disease locus, or a new genetic marker, and a linkage group previously established from a reference panel of families. The method is illustrated by an application to simulated pedigree data in a situation akin to Duchenne muscular dystrophy. These results show that considerable economy and efficiency can be brought to the mapping endeavor by resorting to appropriate strategies of detecting linkage and by constructing the human genetic map on a common reference panel of families.